Zymeworks and Jazz Pharmaceuticals have received the US Food and Drug Administration (FDA) accelerated approval for Ziihera (zanidatamab-hrii) in the treatment of biliary tract cancer (BTC).
The approval is for Ziihera 50mg/mL for injection, for intravenous use in the treatment of adults with previously treated, unresectable or metastatic HER2-positive (IHC 3+) BTC, as identified by an FDA-approved test.
Ziihera, a dual HER2-targeted bispecific antibody, is the first chemotherapy-free treatment for BTC patients. It is being developed by Jazz Pharmaceuticals and BeiGene under licence agreements with Zymeworks.
Zymeworks has earned a $25m milestone payment following FDA approval for BTC. Additionally, the biotechnology firm is eligible for up to $500m in regulatory milestones, $862.5m in commercial milestones, and tiered royalties of 10% to 20% of net sales by Jazz.
The drug previously received breakthrough therapy designation from the FDA for this indication.
Zymeworks chief scientific officer Paul Moore said: “This approval exemplifies our team’s exceptional scientific capabilities to translate from an initial hypothesis for dual-HER2 blockade to a breakthrough treatment that offers new hope for patients with unresectable or metastatic HER2-positive BTC with limited treatment options and few approved therapies.”
The FDA approval is supported by data from the HERIZON-BTC-01 trial, a Phase 2b clinical trial for previously treated HER2-positive BTC.
The trial evaluated zanidatamab as a single agent, using Roche Diagnostic’s PATHWAY anti-HER-2/neu (4B5) Rabbit Monoclonal Primary Antibody as a companion diagnostic.
The trial successfully met its primary endpoint, demonstrating a confirmed objective response rate (cORR) as assessed by an independent central review (ICR).
Ziihera showed a 52% objective response rate (ORR) and a median duration of response (DOR) of 14.9 months.
The continued approval may be contingent on further trials verifying clinical benefit in a confirmatory trial.
Jazz Pharmaceuticals chief medical officer and research and development global head and executive vice president Rob Iannone said: “The approval of Ziihera, which previously received Breakthrough Therapy Designation from the FDA for this indication, is an important advance and offers the first and only dual HER2-targeted bispecific antibody and chemotherapy-free treatment for patients living with BTC.”
The Phase 3 HERIZON-BTC-302 trial is evaluating zanidatamab with standard therapy for first-line HER2-positive BTC.
Zanidatamab is also being tested in other cancers, including gastroesophageal adenocarcinomas (GEAs) and metastatic breast cancer (mBC).
The HERIZON-GEA-01 trial explores zanidatamab plus chemotherapy for advanced HER2-positive GEAs, with results expected in Q2 2025. The EmpowHER-303 trial targets HER2-positive mBC.
